Mapping the developing human immune system across organs
Chenqu Suo, Emma Dann, Issac Goh, Laura Jardine, Vitalii Kleshchevnikov, Jong-Eun Park, Rachel A. Botting, Emily Stephenson, Justin Engelbert, Zewen Kelvin Tuong, Krzysztof Polański, Nadav Yayon, Chuan Xu, Ondřej Suchánek, Rasa Elmentaite, Cecilia Domínguez Conde, Peng He, Sophie Pritchard, Mohi Miah, Corina Moldovan, Alexander S. Steemers, Pavel Mazin, Martin Prete, Dave Horsfall, John C. Marioni, Menna R. Clatworthy, Muzlifah Haniffa, Sarah A. Teichmann
Abstract
Single-cell genomics studies have decoded the immune cell composition of several human prenatal organs but were limited in describing the developing immune system as a distributed network across tissues. We profiled nine prenatal tissues combining single-cell RNA sequencing, antigen-receptor sequencing, and spatial transcriptomics to reconstruct the developing human immune system. This revealed the late acquisition of immune-effector functions by myeloid and lymphoid cell subsets and the maturation of monocytes and T cells before peripheral tissue seeding. Moreover, we uncovered system-wide blood and immune cell development beyond primary hematopoietic organs, characterized human prenatal B1 cells, and shed light on the origin of unconventional T cells. Our atlas provides both valuable data resources and biological insights that will facilitate cell engineering, regenerative medicine, and disease understanding.